{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T06:22:52Z","timestamp":1774678972440,"version":"3.50.1"},"reference-count":41,"publisher":"Microbiology Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,5,1]]},"abstract":"<jats:p>Tuberculous meningitis (TBM) is the most devastating form of meningitis and prompt diagnosis holds the key to its management. Conventional microbiology has limited utility and nucleic acid-based methods have not been widely accepted for various reasons. In view of the paucibacillary nature of cerebrospinal fluid (CSF) and the recent demonstration of free <jats:italic>Mycobacterium tuberculosis<\/jats:italic> DNA in clinical specimens, the present study was designed to evaluate the utility of CSF \u2018filtrates\u2019 for the diagnosis of TBM using PCR. One hundred and sixty-seven CSF samples were analysed from patients with \u2018suspected\u2019 TBM (<jats:italic>n<\/jats:italic>=81) and a control group including other cases of meningitis or neurological disorders (<jats:italic>n<\/jats:italic>=86). CSF \u2018sediments\u2019 and \u2018filtrates\u2019 were analysed individually for <jats:italic>M. tuberculosis<\/jats:italic> DNA by quantitative real-time PCR (qRT-PCR) and conventional PCR. Receiver-operating characteristic curves were generated from qRT-PCR data and cut-off values of 84 and 30 were selected for calling a \u2018filtrate\u2019 or \u2018sediment\u2019 sample positive, respectively. Based on these, TBM was diagnosed with 87.6\u200a% and 53.1\u200a% sensitivity (<jats:italic>P<\/jats:italic> &lt;0.001) in \u2018filtrates\u2019 and \u2018sediments\u2019, respectively, and with 92\u200a% specificity each. Conventional <jats:italic>devR<\/jats:italic> and IS<jats:italic>6110<\/jats:italic> PCR were also significantly more sensitive in \u2018filtrates\u2019 versus \u2018sediments\u2019 (sensitivity of 87.6\u200a% and 85.2\u200a% vs 31\u200a% and 39.5\u200a%, respectively; <jats:italic>P<\/jats:italic> &lt;0.001). The qRT-PCR test yielded a positive likelihood ratio of 11 and 6.6 by analysing \u2018filtrate\u2019 and \u2018sediment\u2019 fractions, respectively, which establishes the superiority of the \u2018filtrate\u2019-based assay over the \u2018sediment\u2019 assay. PCR findings were separately verified in 10 confirmed cases of TBM, where <jats:italic>M. tuberculosis<\/jats:italic> DNA was detected using <jats:italic>devR<\/jats:italic> PCR assays in \u2018sediment\u2019 and \u2018filtrate\u2019 fractions of all samples. From this study, we conclude that (i) CSF \u2018filtrates\u2019 contain a substantial amount of <jats:italic>M. tuberculosis<\/jats:italic> DNA and (ii) \u2018filtrates\u2019 and not \u2018sediments\u2019 are likely to reliably provide a PCR-based diagnosis in \u2018suspected\u2019 TBM patients.<\/jats:p>","DOI":"10.1099\/jmm.0.006015-0","type":"journal-article","created":{"date-parts":[[2009,4,15]],"date-time":"2009-04-15T17:38:13Z","timestamp":1239817093000},"page":"616-624","source":"Crossref","is-referenced-by-count":51,"title":["Efficient diagnosis of tuberculous meningitis by detection of Mycobacterium tuberculosis DNA in cerebrospinal fluid filtrates using PCR"],"prefix":"10.1099","volume":"58","author":[{"given":"Sagarika","family":"Haldar","sequence":"first","affiliation":[{"name":"Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neera","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Department of Pediatrics, Dr Ram Manohar Lohia Hospital, New Delhi 110001, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V. K.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Department of Pediatrics, Dr Ram Manohar Lohia Hospital, New Delhi 110001, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaya Sivaswami","family":"Tyagi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0962-8479(94)90045-0","article-title":"Diagnostic criteria for tuberculous meningitis and their validation","volume":"75","author":"Ahuja","year":"1994","journal-title":"Tuber Lung Dis"},{"key":"R2","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1128\/JCM.43.5.2471-2473.2005","article-title":"Comparison of six methods of extracting Mycobacterium tuberculosis DNA from processed sputum for 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